Low-dose dobutamine stress gated blood pool SPECT assessment of left ventricular contractile reserve in ischemic cardiomyopathy: a feasibility study.

PURPOSE: The purpose of the present study was to evaluate the feasibility of gated blood pool single-photon emission computed tomography (GBPS) with low-dose dobutamine (LDD) stress test, performed on a single-photon emission computed tomography (SPECT) camera equipped with cadmium-zinc-telluride (CZT) solid-state detectors, in assessing of left ventricle (LV) contractile reserve in patients with ischemic cardiomyopathy (ICM). METHODS: A total of 52 patients (age 59 ± 7.2 years, 47 men and 5 women) with ICM and a control group of 10 patients without obstructive coronary artery lesion underwent GBPS and transthoracic echocardiography (TTE) at rest and during LDD stress test (5, 10, 15 µg/kg/min). The duration of each GBPS step was 5 min. Stress-induced changes in LV ejection fraction (ΔLVEF), peak ejection rate, LV volumes, and mechanical dyssynchrony (phase histogram standard deviation, phase histogram bandwidth and entropy) obtained with GBPS were estimated. RESULTS: All GBPS indices except end-diastolic volume showed significant dynamics during stress test in both groups. The majority of parameters in ICM patients showed significant changes at a dobutamine dose of 10 µg/kg/min as compared to the rest study. Seventeen percent of ICM patients, but none from the control group, showed a decrease in LVEF during stress, accompanied by a significant increase in entropy. The intra- and inter-observer reproducibility was excellent for both rest and stress studies. There was a moderate correlation (r = 0.5, p = 0.01) between GBPS and TTE, with a mean difference value of - 1.7 (95% confidence interval - 9.8; 6.4; p = 0.06) in ΔLVEF. CONCLUSION: Low-dose dobutamine stress GBPS performed with high-efficiency CZT-SPECT cameras can be performed for evaluating stress-induced changes in LV contractility and dyssynchrony with lower acquisition time. A dobutamine dose of 10 µg/kg/min can potentially suffice to detect stress-induced changes in patients with ICM during GBPS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04508608 (August 7, 2020).

Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study).

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.

The Value of Stress-Gated Blood Pool SPECT in Predicting Early Postoperative Period Complications in Ischemic Cardiomyopathy Patients: Focus on Mechanical Dyssynchrony.

(1) Objective: The objective of this study was to assess the prognostic value of stress-gated blood pool SPECT (GBPS) estimates in patients with ischemic cardiomyopathy (ICM) in the early postoperative period. (2) Methods: A total of 57 patients (age 59.7 ± 6.6, 47 men) with ICM and LV ejection fraction (30 [27.5; 35]%) were enrolled in the study. Before surgical treatment, all patients underwent GBPS (rest-stress, dobutamine doses of 5/10/15 µg/kg/min). Stress-induced changes in left ventricular (LV) ejection fraction, peak ejection rate, volumes, and mechanical dyssynchrony (phase histogram standard deviation, phase entropy (PE), and phase histogram bandwidth) were estimated. Two-dimensional transthoracic echocardiography was performed baseline. Serum levels of NT-proBNP were analyzed with enzyme-linked immunoassay. (3) Results: After surgical treatment, patients were divided into two groups, one, with death, the need for an intra-aortic balloon pump (IABP) or/and inotropic support with a stay in the intensive care unit for more than two days and two, without complications in the early postoperative period (EPOP). Complicated EPOP (CEPOP) was observed in 17 (30%) patients (death-2, IABP-4, extra inotropic support in intensive care unit-11), and 40 patients had no complications (NCEPOP). GBPS showed differences in LV EDV (mL) (321 [268; 358] vs. 268 [242; 313], p = 0.02), LV ESV (mL) (242 [201; 282] vs. 196 [170; 230], p = 0.005), and stress-induced changes in PE (1 (-2; 3) vs. -2 (-4; 0), p = 0.02). Aortic cross-clamp time and stress-induced changes in PE between rest and dobutamine dose of 10 µg/kg/min were the only independent predictors of CEPOP. An increase in LV entropy ≥ 1 on the dobutamine dose of 10µg/kg/min in comparison to rest investigation showed AUC = 0.853 (sensitivity = 62%, specificity = 90%, PPV = 71%; NPV = 85%; p < 0.0001). Conclusion: Stress-induced changes in PE obtained during low-dose dobutamine GBPS are associated with a complicated course of the early postoperative period after surgical treatment for ICM.

Morphological and immunological markers of repeated heart remodeling after surgical reconstruction of the left ventricle in ischemic cardiomyopathy.

INTRODUCTION: Effective treatment of patients with ischemic cardiomyopathy (ICM) is one of the most challenging issues in modern cardiac surgery. The aim of this study was to assess the state of cardiomyocytes and myocardial extracellular matrix, as well as to identify informative markers of an unfavorable prognosis for surgical treatment of ICM. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent surgical treatment of ICM between 2011 and 2018 at a single center. Patients were divided into groups depending on the presence of repeated left ventricle (LV) remodeling in one-year follow-up after surgical reconstruction of the LV in ICM patients. RESULTS: A total of 45 patients with ICM were reviewed. The mean age of the patients was 57.9 ± 7.8 years. According to the results of the study, the area of cardiomyocyte nuclei differed statistically significantly among the regions with varying degrees of impaired local contractility (p = 0.042). According to the results of the pairwise comparison in dyskinetic areas of the myocardium, the area of cardiomyocyte nuclei was higher than in normokinetic areas (p = 0.042). A moderate positive correlation was found between the LV ejection fraction measured in one-year follow-up period after surgery and the number of CD163-positive cells (p = 0.012). CONCLUSION: In the myocardium of patients with LV reverse remodeling in the long-term postoperative period, perivascular fibrosis occurs more frequently than in patients with progressive LV remodeling. The number of M2-anti-inflammatory macrophages prevails in the myocardium of the patients with reverse remodeling compared with patients with progressive remodeling.

Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy.

BACKGROUND: The angiopoietic endothelial dysfunction in ischemic cardiomyopathy (ICMP) remains unexplored. AIM: The identification of the imbalance of endothelial dysfunction mediators and the number of endothelial progenitor (EPC) and desquamated (EDC) cells in patients with coronary heart disease (CHD) with and without ICMP. METHODS: A total of 87 patients (47 with ICMP and 40 without ICMP) were observed. The content of EPCs (CD14+CD34+VEGFR2+) in vein blood and EDCs (CD45-CD146+) in the blood from the coronary sinus and cubital vein was determined by flow cytometry. The contents of HIF-1α and HIF-2α in vein blood as well as that of ADMA and endothelin-1 in sinus plasma and angiopoietin-2, MMP-9 and galectin-3 in both samples were assessed using ELISA, and VEGF, PDGF, SDF-1 and MCP-1 contents using immunofluorescence. RESULTS: ADMA and endothelin-1 levels in the sinus blood were comparable between the patient groups; a deficiency of HIF-1α and excess of HIF-2α were detected in the vein blood of ICMP patients. The EDC content in the vein blood increased in CHD patients regardless of ICMP, and the concentrations of VEGF-A, VEGF-B, PDGF, MCP-1, angiopoietin-2, and MMP-9 were normal. In ICMP patients, vein blood was characterized by an excess of galectin-3 and sinus blood by an excess of EDCs, angiopoietin-2, MMP-9 and galectin-3. CONCLUSION: ICMP is accompanied by angiopoietic endothelial dysfunction.

Endothelial Function and Hypoxic-Hyperoxic Preconditioning in Coronary Surgery with a Cardiopulmonary Bypass: Randomized Clinical Trial.

A hypoxic-hyperoxic preconditioning (HHP) may be associated with cardioprotection by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients (n = 120) were randomly assigned to an HHP and a control group. A safe, inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 min) was determined by measuring the anaerobic threshold. At the hyperoxic phase, a 75-80% oxygen fraction was used for 30 min. The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs. 23 (41.1%), p = 0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low for more than 24 h in the control group. The endothelial damage markers appeared to be predictors of postoperative complications. The HHP with individual parameters based on the anaerobic threshold is a safe procedure, and it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial.

OBJECTIVE: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of nitric oxide (NO) supplementation to the CPB circuit on the development of cardiac surgery-associated AKI. METHODS: This prospective randomized controlled study included 96 patients with moderate risk of renal complications who underwent elective cardiac surgery with CPB. The study protocol was registered at ClinicalTrials.gov (identifier NCT03527381). Patients were randomly allocated to either NO supplementation to the CPB bypass circuit (NO treatment group; n = 48) or usual care (control group; n = 48). In the NO treatment group, 40-ppm NO was administered during the entire CPB period. The primary outcome was the incidence of AKI. RESULTS: NO treatment was associated with a significant decrease in AKI incidence (10 cases [20.8%] vs 20 cases [41.6%] in the control group; relative risk, 0.5; 95% confidence interval, 0.26-0.95; P = .023) and a higher median urine output during CPB (2.6 mL/kg/h [interquartile range (IQR), 2.1-5.08 mL/kg/h] vs 1.7 mL/kg/h [IQR, 0.80-2.50 mL/kg/h]; P = .0002). The median urinary neutrophil gelatinase-associated lipocalin level at 4 hours after surgery was significantly lower in the NO treatment group (1.12 ng/mL [IQR, 0.75-5.8 ng/mL] vs 4.62 ng/mL [IQR, 2.02-34.55 ng/mL]; P = .005). In the NO treatment group, concentrations of NO metabolites were significantly increased at 5 minutes postclamping, at 5 minutes after declamping, and at the end of the operation. Concentrations of proinflammatory and anti-inflammatory mediators and free plasma hemoglobin did not differ significantly between the 2 groups. CONCLUSIONS: NO administration in patients at moderate risk of renal complications undergoing elective cardiac surgery with CPB was associated with a lower incidence of AKI.

Results of reconstructive interventions in patients with ischemic cardiomyopathy.

BACKGROUND: Effective treatment of patients with ischemic cardiomyopathy is one of the most difficult issues in contemporary cardiac surgery. The aim of this study was to evaluate the long-term effectiveness of reconstructive interventions on the left ventricle during chronic heart failure in patients with ischemic cardiomyopathy. METHODS: Between March 2013 and December 2017, 178 patients underwent surgical treatment for ischemic cardiomyopathy. Isolated coronary artery bypass grafting was compared with coronary artery bypass grafting with left ventricular reconstruction, using propensity score matching analysis. The primary endpoints of the study were hospital mortality and long-term survival. RESULTS: After propensity score matching, 29 pairs of patients were compared. The 30-day hospital mortality was comparable (6.8% versus 6.8%, p = 0.952), the average follow-up was 37.4 ± 12.6 months, with no statistically significant difference in mortality from all causes (p = 0.352). After coronary artery bypass in combination with left ventricular reconstruction, patients showed a statistically significant decrease in clinical and functional indicators of chronic heart failure compared to those who had coronary artery bypass grafting alone, in terms of peak oxygen consumption (15.3 versus 13.5 mL·kg-1·min-1, p = 0.043) and N-terminal pro-brain natriuretic peptide concentrations (298.6 versus 461.1 pg·mL-1, p = 0.032). CONCLUSIONS: Compared to isolated coronary artery bypass, coronary artery bypass in combination with left ventricular reconstruction for the treatment of ischemic cardiomyopathy leads to a significant decrease in the clinical and functional parameters of chronic heart failure in the long-term postoperative period.

Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial.

OBJECTIVES: The aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: A total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS). RESULTS: NO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 ± 0.39 ng/mL versus 2.41 ± 0.55 ng/mL, respectively (P = .001). The CK-MB value was significantly lower in NO-treated group compared with the control group 24 hours after surgery: 47.69 ± 8.08 U/L versus 62.25 ± 9.78 U/L, respectively (P = .001); and the VIS was significantly lower in the NO-treated group 6 hours after the intervention. CONCLUSIONS: NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with lower levels of VIS and cardiospecific blood markers cTnI and CK-MB.

Distal aortic remodelling after the standard and the elongated frozen elephant trunk procedure.

OBJECTIVES: The aim of this study was to evaluate abdominal aortic remodelling after the standard compared with the elongated frozen elephant trunk (FET) technique in patients with aortic dissection. METHODS: Twenty-six patients underwent surgery and were randomized into 2 groups. Fifteen patients were treated with the standard FET technique. Eleven patients were treated with the advanced FET technique using an additional thoracic stent graft implanted down to the coeliac artery, within 30 days after the first stent graft implantation. Preoperative and postoperative and 5-year follow-up computed tomography aortic scans were obtained along the stent graft (A), between the distal edge of the graft and the coeliac trunk (B) and at the abdominal aorta (C). RESULTS: In the standard FET group, positive and stable aortic remodelling occurred in segments A (100%), B (87%) and C (87%). Negative remodelling was found in 2/15 (13%) patients; 1 patient had an endovascular reintervention. In the elongated FET group, positive and stable remodelling were observed in segments A (100%), B (100%) and C (90.9%). Negative remodelling occurred in 1/11 (9.1%) patients. No reintervention was required. Cumulative survival, freedom from negative remodelling and distal aortic reintervention in the standard FET group and the elongated FET group were 72 vs 100% (P = 0.29); 67.5 vs 80% (P = 0.58) and 75 vs 100% (P = 0.61), respectively. CONCLUSIONS: The standard FET technique is an adequate measure to induce false lumen thrombosis and improve abdominal aortic remodelling. The elongated FET technique seems to be superior to the standard FET procedure in terms of freedom from aortic remodelling and the distal reintervention rate.

The risk of spinal cord injury during the frozen elephant trunk procedure in acute aortic dissection.

OBJECTIVES: The aim of the study was to access the extended occlusion of the intercostal arteries by a stent graft in the development of postoperative spinal cord injury during aortic arch surgery using the frozen elephant trunk technique. METHODS: A total of 37 consecutive patients underwent total aortic arch surgery using the frozen elephant trunk technique between March 2012 and July 2017. The mean age of the patients was 54.7 ± 10.5 years. Type A and Type B aortic dissections were the indications for surgery. Moderate hypothermia and antegrade cerebral perfusion via the innominate artery were utilized. The mean diameter of the implanted stent graft was 27.7 ± 2 mm (range 24-30 mm). RESULTS: No permanent spinal cord injuries occurred. The distal edge of the stent graft was in the T7-T12 range. Its lower edge was implanted at the T9-T12 level in 25 (67.6%) cases. Preoperatively, the mean number of intercostal arteries was 10 ± 1 on the left side and 10 ± 2 on the right side (P = 0.59). Postoperatively, the mean number of open segmental arteries was 3 ± 2 on the left and 4 ± 1 on the right (P = 0.003). CONCLUSIONS: The frozen elephant trunk procedure is associated with the occlusion of most (two-thirds) of the intercostal arteries. Maintenance of adequate blood flow in the subclavian and iliac arteries is an integral prerequisite for a favourable outcome. The level of the deployment of the distal edge of the stent graft does not play a defining role.

Hybrid treatment of aortic dissection associated with Kommerell's diverticulum.

This clinical case demonstrates a successful simultaneous approach for Type B aortic dissection in association with Kommerell's diverticulum using an E-vita OPEN PLUS Hybrid prosthesis. Computed tomography in the early postoperative period and after a 6-month follow-up showed favourable surgical outcomes.

Causes of repeated remodeling of left ventricle after Dor procedure.

OBJECTIVES: To reveal morphological factors causing unfavorable follow-up outcome of surgical treatment of patients with ischemic cardiomyopathy (ICMP) and with left ventricle (LV) aneurysm according to the data of intraoperative biopsies of LV myocardium and right atrium (RA) auricle. METHODS: The object of the study was to examine biopsy material of LV myocardium and RA auricle from 36 patients with ICMP. Clinical criteria of patients' inclusion into the study were: ESI LV >80 ml/m(2), EDP LV >30 mmHg, LV EF <40%, presence of akinetic and dyskinetic areas in LV, angina of II-IV class CCS, heart failure of II-IV class NYHA. The following morphometrical parameters were estimated for revelation of postoperative remodeling risk factors: parenchymal-stromal ratio (PSR), trophic index (TI), pericapillar diffusion zone (PDZ), Kernogan index (KI) and specific volume of granules of natriuretic factor (NUF) in atrial cardiomyocytes. RESULTS: In all the patients LV EF increased significantly (from 36.4+/-4.1% to 46.3+/-4.2%) (P<0.05) in the early postoperative period; LV EDI decreased (from 139.3+/-11.2 ml/m(2) to 108.4+/-8.9 ml/m(2)) (P<0.05). In the follow-up period (one year) all the patients were divided into two groups: in 28 patients (the 1st group) volume of the cavity, contractile function of LV remained satisfactory. In the other eight patients (the 2nd group) there was significant decrease of LV EF (up to 33.9+/-10.2%) due to increase of LV EDI [up to 129.2+/-10.1 ml/m(2) (P<0.05)]. Grade of MR preoperatively was 1.21+/-0.5 and 1.47+/-0.9, correspondingly, for the patients with positive and negative changes in the follow-up postoperative period. Drawing morphological parallels of postoperative heart remodeling in patients with ICMP showed that diffusive, lymphocytic-macrophage inflammatory infiltration of myocardial stroma in combination with severe fibrosis (PSR<1.5), low TI (<0.015) and greater value of PDZ (>1000 microm) and KI (>1.6) of LV myocardium are the factors connected with unfavorable follow-up results of surgical treatment. Moreover, we showed an inverse correlative relationship between content of NUF granules in the cardiomyocytes of RA auricle and the outcomes of the Dor procedure. CONCLUSIONS: Thus, a combination of the foregoing features is a morphological predictor of postoperative heart remodeling in patients with ICMP.